AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

Simultaneously achieving high energy-storage density and power density under low electric fields in NBT-based ceramics

Aiming at the problem that power density and energy density are difficult to obtain simultaneously under low field, a novel composition (1-x)Na_0·5Bi_0·5TiO₃-xBaZn_1/3Ta_2/3O₃((1-x)NBT-xBZT) was designed and fabricated via solid-state methods. With the addition of BZT, the crystal lattice, structural symmetry, grain size, and dense degree were all increased proved by XRD, Raman, and Archimedes drainage method et al. Because of the enhancement of relaxor behavior, the x=0.10 sample displayed a high permittivity ε_r of 2871±15% and a low dielectric loss tan δ ≤ 0.025 in the wide temperature range of 60–400 ^oC. This ceramic also showed maximum recoverable energy density W_d (2.07 J/cm³) with high efficiency η (71.5%) under a low field of 150 kV/cm. Moreover, pulse discharge testing proved that this ceramic possessed both a significant discharge energy density W_D (0.96 J/cm³) and a record high power density P_D (108.54 MW/cm³). This work provided a promising material for high power and energy applications.     

[2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists

Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site.     

Femtosecond Ti: Sa ultra short-pulse laser irradiation effects on the properties and morphology of the zirconia surface after ageing

Femtosecond pulses from a Ti:Sapphire laser were used to irradiate specimens of yttria-stabilised (35% mol) tetragonal zirconia (Y-TZP) with the purpose of studying the effects of the irradiations on their surface properties and morphology after ageing. Zirconia disks were divided into eight groups (n = 32) according to their surface treatment and subsequent ageing: Control: no treatment; sandblasting: Al₂O₃ sandblasting 50 μm; and ultrashort laser pulses irradiation with 25 μJ pulses, considering two different scanning steps based on the width between two grooves. These groups were duplicated and submitted to ageing. The surfaces were analysed using scanning electron microscopy (SEM), and X-ray diffraction. A finite element analysis, a biaxial flexure test, as well as fractographic and Weibull analyses, were performed. The strengths of the disks were statistically different for the treatment factor, and the principal stresses seemed to be concentrated at the centre of the specimens, as predicted by the computer simulations. Ageing decreased the strengths for all groups and increased the Weibull modulus for the laser group with the 40 μm-width between two grooves. The sandblasting group presented the highest monoclinic phase peak. Although the most significant strength was found within the sandblasting group, the phase transformation was favourable to the laser groups. The Weibull modulus was higher for the laser group with the 60 μm-width between two grooves, confirming the highest homogeneity of its failure distribution. Regardless of the surface treatment, strength was decreased with ageing in all groups. The femtosecond Ti:Sa ultra-short pulse laser irradiation can be suggested as an alternative to the gold standard sandblasting in long-term Y-TZP zirconia rehabilitations, such as crowns and veneers.     

A novel fabrication procedure for producing high strength hydroxyapatite ceramic scaffolds with high porosity

Hydroxyapatite (HA) scaffolds were fabricated using the space holder method with a pressureless sintering process in a systematically developed manner at different fabrication stages to increase the strength of the scaffold at high porosity. Polyvinyl alcohol (PVA) and Polymethyl methacrylate (PMMA) were used as binders and space holder agents, respectively. The physical properties of the HA scaffolds were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), linear shrinkage test, and porosity measurements. The mechanical properties of the HA scaffolds were analyzed using compressive strength measurements. The results revealed that the HA scaffold met the expected quality requirements with a compressive strength of 2.2 MPa at a porosity of 65.6% with pore sizes distributed in the range of 126–385 μm. The shrinkage of the scaffold diameter occurred by 20.27%, this diameter shrinkage predominantly to the shrinkage of the HA scaffold caused by sintering. Besides, suspect that a higher PMMA concentration causes pore size shrinkage upon sintering. The formation of pore interconnections was evidenced by SEM observations and the ‘translucent light method’ developed in this study. The results of the scaffold phase test using XRD showed that the final scaffold consisted only of the HA phase, as the PVA and PMMA phases burned out during the sintering process.     

磨料有序排布电镀砂轮的制备及其把持力研究

为解决电镀砂轮磨削加工中容屑空间不足的问题，采用点胶微粘接的方法制备了磨料有序排布的电镀砂轮，分析了磨料粘接效果和镀层力学性能。通过SEM分析了磨料/镀层/导电胶的结合界面，并进行了干磨削试验。研究结果表明，直径约为磨料粒径40%的胶点可粘接住磨料，单个胶点上粘接多颗磨料的占比小于6%；双脉冲电镀工艺制备的镀层显微硬度大于500HV，表层残余应力小于100MPa，磨料/镀层/导电胶之间的界面贴合紧密，无明显缺陷；砂轮在磨削时没有出现磨料脱落现象。     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Intrinsic Defect Limit to the Growth of Orthorhombic HfO2 and (Hf,Zr)O2 with Strong Ferroelectricity: First-Principles Insights

It is believed that promoting the fraction of ferroelectric orthorhombic phase (o-phase) through O-poor growth conditions can increase the spontaneous polarization of HfO₂ and (Hf,Zr)O₂ thin films. However, the first-principles calculations show that the growth may be limited by the easy formation of point defects in the orthorhombic and tetragonal phases of HfO₂, ZrO₂, and (Hf,Zr)O₂. Their dominant defects, O interstitial (O_i) under O-rich conditions and O vacancy (V_O) under O-poor condition, have low formation energies and quite high density (10¹⁶–10¹⁹ cm⁻³ for 800–1400 K growth temperature). Especially, O_i has negative formation energy in tetragonal HfO₂ under O-rich condition, causing non-stoichiometry and limiting the crystalline-seed formation during o-phase growth. High-density defects can cause disordering of dipole moments and increase leakage current, both diminishing the polarization. These results explain the experimental puzzle that the measured polarization is much lower than the ideal value even in O-poor thin films and highlight that controlling defects is as important as promoting the o-phase fraction for enhancing ferroelectricity. The O-intermediate condition (average of O-rich and O-poor conditions) and low growth temperature are proposed for fabricating HfO₂ and (Hf,Zr)O₂ with fewer defects, lower leakage current, and stronger ferroelectricity, which challenges the belief that O-poor condition is optimal.